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1.
Geriatr Nurs ; 58: 76-86, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38781628

RESUMEN

This systematic review aimed to describe the characteristics of instruments that assess eating ability and/or mealtime behaviors in persons living with dementia, and evaluate their psychometric properties. Five databases were searched for relevant records between 1/1/1980 and 5/25/2023. Records included instruments assessing eating ability and/or mealtime behaviors of people with dementia. The psychometric quality of the instruments was evaluated using the Psychometric Assessment for Self-report and Observational Tools (PAT). 45 eligible instruments were identified from 115 records. While 38 instruments were scored as having low psychometric quality, 7 had moderate quality. Edinburgh Feeding Evaluation in Dementia (EdFED), Mealtime Difficulty Scale for older adults with Dementia (MDSD), and Dementia Hyperphagic Behavior Scale (DHBS) were scored as having the highest quality (total PAT score = 9). Further refinement of existing instruments and additional psychometric testing in larger, diverse samples will improve pragmatic use in dementia mealtime care research and practice.

2.
Cell Biochem Funct ; 41(6): 696-703, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37322603

RESUMEN

Curcumin is a natural polyphenol that is extracted from the rhizomes of the turmeric plant (Curcuma longa), a member of the ginger family. It has been used for centuries in traditional Indian and Chinese medicine for its medicinal properties, including anti-inflammatory, antioxidant and antitumor effects. SVCT2 (Solute Carrier Family 23 Member 2, also known as SLC23A2) is a protein that plays a role in the transport of Vitamin C (Ascorbic Acid) into cells. SVCT2 plays an important role in tumor progression and metastasis, however, the molecular mechanisms of curcumin on SVCT2 have not been studied to date. Curcumin treatment inhibited proliferation and migration of cancer cells in a dose dependent manner. We found that curcumin reduced the expression of SVCT2 in cancer cells with a wild type p53, but not in those with a mutant type of p53. SVCT2 downregulation also reduced the MMP2 activity. Taken together, our results indicate that curcumin inhibited human cancer cell growth and migration by regulating SVCT2 through a downregulating p53. These findings provide new insights into the molecular mechanisms of curcumin's anticancer effects and potential therapeutic strategies for the treatment of metastatic migration.


Asunto(s)
Curcumina , Neoplasias , Transportadores de Sodio Acoplados a la Vitamina C , Humanos , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Curcumina/farmacología , Regulación hacia Abajo , Neoplasias/tratamiento farmacológico , Proteína p53 Supresora de Tumor , Transportadores de Sodio Acoplados a la Vitamina C/efectos de los fármacos
3.
Angew Chem Int Ed Engl ; 59(28): 11540-11549, 2020 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-32239636

RESUMEN

As agonists of TLR7/8, single-stranded RNAs (ssRNAs) are safe and promising adjuvants that do not cause off-target effects or innate immune overactivation. However, low stability prevents them from mounting sufficient immune responses. This study evaluates the adjuvant effects of ssRNA derived from the cricket paralysis virus intergenic region internal ribosome entry site, formulated as nanoparticles with a coordinative amphiphile, containing a zinc/dipicolylamine complex moiety as a coordinative phosphate binder, as a stabilizer for RNA-based adjuvants. The nanoformulated ssRNA adjuvant was resistant to enzymatic degradation in vitro and in vivo, and that with a coordinative amphiphile bearing an oleyl group (CA-O) was approximately 100 nm, promoted effective recognition, and improved activation of antigen-presenting cells, leading to better induction of neutralizing antibodies following single immunization. Hence, CA-O may increase the efficacy of ssRNA-based adjuvants, proving useful to meet the urgent need for vaccines during pathogen outbreaks.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Células Presentadoras de Antígenos/inmunología , Composición de Medicamentos , Inmunidad Humoral/efectos de los fármacos , Nanotecnología , ARN/química , Adyuvantes Inmunológicos/química , Animales , Humanos
4.
Nano Lett ; 18(7): 4279-4284, 2018 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-29863365

RESUMEN

Enzymatic synthesis of RNA nanostructures is achieved by isothermal rolling circle transcription (RCT). Each arm of RNA nanostructures provides a functional role of Dicer substrate RNA inducing sequence specific RNA interference (RNAi). Three different RNAi sequences (GFP, RFP, and BFP) are incorporated within the three-arm junction RNA nanostructures (Y-RNA). The template and helper DNA strands are designed for the large-scale in vitro synthesis of RNA strands to prepare self-assembled Y-RNA. Interestingly, Dicer processing of Y-RNA is highly influenced by its physical structure and different gene silencing activity is achieved depending on its arm length and overhang. In addition, enzymatic synthesis allows the preparation of various Y-RNA structures using a single DNA template offering on demand regulation of multiple target genes.


Asunto(s)
ARN Helicasas DEAD-box/genética , Nanoestructuras/química , ARN/biosíntesis , Ribonucleasa III/genética , Transcripción Genética , ARN Helicasas DEAD-box/química , ADN/química , Silenciador del Gen , Humanos , Conformación de Ácido Nucleico , ARN/química , ARN/genética , Interferencia de ARN , Ribonucleasa III/química
5.
Adv Sci (Weinh) ; 11(18): e2307541, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38447169

RESUMEN

The development of in vitro transcribed mRNA (IVT mRNA)-based therapeutics/vaccines depends on the management of IVT mRNA immunogenicity. IVT mRNA, which is used for intracellular protein translation, often triggers unwanted immune responses, interfering with protein expression and leading to reduced therapeutic efficacy. Currently, the predominant approach for mitigating immune responses involves the incorporation of costly chemically modified nucleotides like pseudouridine (Ψ) or N1-methylpseudouridine (m1Ψ) into IVT mRNA, raising concerns about expense and the potential misincorporation of amino acids into chemically modified codon sequences. Here, an Additional Chimeric Element incorporated mRNA (ACE mRNA), a novel approach incorporating two segments within a single IVT mRNA structure, is introduced. The first segment retains conventional IVT mRNA components prepared with unmodified nucleotides, while the second, comprised of RNA/DNA chimeric elements, aims to modulate immunogenicity. Notably, ACE mRNA demonstrates a noteworthy reduction in immunogenicity of unmodified IVT mRNA, concurrently demonstrating enhanced protein expression efficiency. The reduced immune responses are based on the ability of RNA/DNA chimeric elements to restrict retinoic acid-inducible gene I (RIG-I) and stimulator of interferon genes (STING)-mediated immune activation. The developed ACE mRNA shows great potential in modulating the immunogenicity of IVT mRNA without the need for chemically modified nucleotides, thereby advancing the safety and efficacy of mRNA-based therapeutics/vaccines.


Asunto(s)
ARN Mensajero , ARN Mensajero/genética , ARN Mensajero/inmunología , ARN Mensajero/metabolismo , Animales , Ratones , Humanos
6.
Adv Sci (Weinh) ; 11(22): e2309917, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38520717

RESUMEN

Lipid nanoparticles (LNPs) exhibit remarkable mRNA delivery efficiency, yet their majority accumulate in the liver or spleen after injection. Tissue-specific mRNA delivery can be achieved through modulating LNP properties, such as tuning PEGylation or varying lipid components systematically. In this paper, a streamlined method is used for incorporating tumor-targeting peptides into the LNPs; the programmed death ligand 1 (PD-L1) binding peptides are conjugated to PEGylated lipids via a copper-free click reaction, and directly incorporated into the LNP composition (Pep LNPs). Notably, Pep LNPs display robust interaction with PD-L1 proteins, which leads to the uptake of LNPs into PD-L1 overexpressing cancer cells both in vitro and in vivo. To evaluate anticancer immunotherapy mediated by restoring tumor suppressor, mRNA encoding phosphatase and tensin homolog (PTEN) is delivered via Pep LNPs to PTEN-deficient triple-negative breast cancers (TNBCs). Pep LNPs loaded with PTEN mRNA specifically promotes autophagy-mediated immunogenic cell death in 4T1 tumors, resulting in effective anticancer immune responses. This study highlights the potential of tumor-targeted LNPs for mRNA-based cancer therapy.


Asunto(s)
Antígeno B7-H1 , Nanopartículas , Fosfohidrolasa PTEN , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Nanopartículas/química , Animales , Ratones , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Femenino , Modelos Animales de Enfermedad , Lípidos/química , Humanos , Línea Celular Tumoral , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/terapia , Ratones Endogámicos BALB C , Inmunoterapia/métodos , Liposomas
7.
Mol Pharm ; 10(10): 3892-902, 2013 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-24024964

RESUMEN

Starch-coated, PEGylated, and heparin-functionalized iron oxide magnetic nanoparticles (DNPH) were successfully synthesized and characterized in detail. The PEGylation (20 kDa) process resulted in an average coating of 430 PEG molecules per nanoparticle. After that, heparin conjugation was carried out to attain the final DNPH platform with 35.4 µg of heparin/mg of Fe. Commercially acquired heparin-coated magnetic nanoparticles were also PEGylated (HP) and characterized for comparison. Protamine was selected as a model protein to demonstrate the strong binding affinity and high loading content of DNPH for therapeutically relevant cationic proteins. DNPH showed a maximum loading of 22.9 µg of protamine/mg of Fe. In the pharmacokinetic study, DNPH displayed a long-circulating half-life of 9.37 h, 37.5-fold longer than that (0.15 h) of HP. This improved plasma stability enabled extended exposure of DNPH to the tumor lesions, as was visually confirmed in a flank 9L-glioma mouse model using magnetic resonance imaging (MRI). Quantitative analysis of the Fe content in excised tumor lesions further demonstrated the superior tumor targeting ability of DNPH, with up to 31.36 µg of Fe/g of tissue (13.07% injected dose (I.D.)/g of tissue) and 7.5-fold improvement over that (4.27 µg of Fe/g of tissue; 1.78% I.D./g of tissue) of HP. Overall, this study shed light on the potential of DNPH to be used as a protein drug delivery platform.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Heparina/química , Imagen por Resonancia Magnética/métodos , Nanopartículas/química , Animales , Compuestos Férricos/química , Glioma/diagnóstico , Glioma/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Nanopartículas/metabolismo , Protaminas/química
8.
Pharm Res ; 30(6): 1642-51, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23543301

RESUMEN

PURPOSE: To test the hypothesis in which polyplex-induced oxidative stress may affect overall transfection efficiency, an antioxidative transfection system minimizing cellular oxidative stress was designed for enhanced transfection. METHODS: An amphiphilic copolymer (PEI-PLGA) was synthesized and used as a micelle-type gene carrier containing hydrophobic antioxidant, α-tocopherol. Cellular oxidative stress and the change of mitochondrial membrane potential after transfection was measured by using a fluorescent probe (H2DCFDA) and lipophilic cationic probe (JC-1), respectively. Transfection efficiency was determined by measuring a reporter gene (luciferase) expression level. RESULTS: The initial transfection study with conventional PEI/plasmid DNA polyplex showed significant generation of reactive oxygen species (ROS). The PEI-PLGA copolymer successfully carried out the simultaneous delivery of α-tocopherol and plasmid DNA (PEI-PLGA/Toco/pDNA polyplex) into cells, resulting in a significant reduction in cellular ROS generation after transfection and helped to maintain the mitochondrial membrane potential (ΔΨ). In addition, the transfection efficiency was dramatically increased using the antioxidative transfection system. CONCLUSIONS: This work showed that oxidative stress would be one of the important factors that should be considered in designing non-viral gene carriers and suggested a possible way to reduce the carrier-mediated oxidative stress, which consequently leads to enhanced transfection.


Asunto(s)
Antioxidantes/farmacología , Vectores Genéticos/genética , Estrés Oxidativo/efectos de los fármacos , Polímeros/farmacología , Antioxidantes/química , Línea Celular Tumoral , ADN/genética , Técnicas de Transferencia de Gen , Células HCT116 , Células Hep G2 , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Iminas/química , Ácido Láctico/química , Luciferasas/química , Luciferasas/genética , Células MCF-7 , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/genética , Micelas , Estrés Oxidativo/genética , Plásmidos/genética , Polietilenos/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/química , Especies Reactivas de Oxígeno/metabolismo , Transfección/métodos , alfa-Tocoferol/química , alfa-Tocoferol/farmacología
9.
Pharm Res ; 30(10): 2445-58, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23344909

RESUMEN

In this review, we discussed the establishment of a so-called "theranostic" system by instituting the basic principles including the use of: [1] magnetic iron oxide nanoparticles (MION)-based drug carrier; [2] intra-arterial (I.A.) magnetic targeting; [3] macromolecular drugs with unmatched therapeutic potency and a repetitive reaction mechanism; [4] cell-penetrating peptide-mediated cellular drug uptake; and [5] heparin/protamine-regulated prodrug protection and tumor-specific drug re-activation into one single drug delivery system to overcome all possible obstacles, thereby achieving a potentially non-invasive, magnetic resonance imaging-guided, clinically enabled yet minimally toxic brain tumor drug therapy. By applying a topography-optimized I.A. magnetic targeting to dodge rapid organ clearance of the carrier during its first passage into the circulation, tumor capture of MION was enriched by >350 folds over that by conventional passive enhanced permeability and retention targeting. By adopting the prodrug strategy, we observed by far the first experimental success in a rat model of delivering micro-gram quantity of the large ß-galactosidase model protein selectively into a brain tumor but not to the ipsi- or contra-lateral normal brain regions. With the therapeutic regimens of most toxin/siRNA drugs to fully (>99.9%) eradicate a tumor being in the nano-molar range, the prospects of reaching this threshold become practically accomplishable.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Sistemas de Liberación de Medicamentos/métodos , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita , Animales , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Humanos , Inyecciones Intraarteriales , Inyecciones Intravenosas , Nanopartículas de Magnetita/administración & dosificación , Nanopartículas de Magnetita/uso terapéutico
10.
Mol Cells ; 46(1): 41-47, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36697236

RESUMEN

The rapid development of mRNA vaccines has contributed to the management of the current coronavirus disease 2019 (COVID-19) pandemic, suggesting that this technology may be used to manage future outbreaks of infectious diseases. Because the antigens targeted by mRNA vaccines can be easily altered by simply changing the sequence present in the coding region of mRNA structures, it is more appropriate to develop vaccines, especially during rapidly developing outbreaks of infectious diseases. In addition to allowing rapid development, mRNA vaccines have great potential in inducing successful antigen-specific immunity by expressing target antigens in cells and simultaneously triggering immune responses. Indeed, the two COVID-19 mRNA vaccines approved by the U.S. Food and Drug Administration have shown significant efficacy in preventing infections. The ability of mRNAs to produce target proteins that are defective in specific diseases has enabled the development of options to treat intractable diseases. Clinical applications of mRNA vaccines/therapeutics require strategies to safely deliver the RNA molecules into targeted cells. The present review summarizes current knowledge about mRNA vaccines/ therapeutics, their clinical applications, and their delivery strategies.


Asunto(s)
Vacunas contra la COVID-19 , Vacunas de ARNm , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/genética , Vacunas de ARNm/administración & dosificación , Sistemas de Lectura Abierta , Pandemias , Estados Unidos
11.
Innov Aging ; 7(5): igad052, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37457804

RESUMEN

Background and Objectives: It is critical to use validated instruments to diagnose and manage chewing and swallowing problems of persons living with dementia. The study aimed to synthesize the characteristics and psychometric quality of instruments that assess the chewing and swallowing abilities of persons living with dementia. Research Design and Methods: The systematic review was used to conduct this study. We searched 5 electric databases for records published from January 1, 1980, to July 8, 2022. Records were eligible if they included any instrument to assess chewing ability or swallowing ability in the dementia population. Eight characteristics of eligible instruments were extracted from the records: (1) development process, (2) operationalized concept/construct, (3) sample and setting, (4) administration method, (5) items, (6) scoring format/interpretation, (7) reliability, and (8) validity. The psychometric assessment for self-report and observational tool was used to evaluate 12 psychometric properties of eligible instruments. Results: In total, 11,074 records were reviewed. Thirty-five eligible instruments, including observational tools, self-report questionnaires, and physiological instruments, were identified from 60 records. All 8 instruments assessing chewing ability were evaluated as having low psychometric quality, and only 3 out of 27 instruments assessing swallowing ability were evaluated as having moderate psychometric quality. Fifteen instruments were tested for only 1 type of psychometric property, limiting the overall evaluation of psychometric evidence. Discussion and Implications: The study findings inform the use and adaptation of appropriate instruments for practice and research. All existing instruments warrant further validation in larger samples to expand use in diverse care settings. This review described and evaluated current instruments measuring chewing and swallowing abilities and potential use in research and clinical practice to plan for and evaluate the effectiveness of mealtime and oral care practice and reduce health-related negative outcomes of persons living with dementia.

12.
Innov Aging ; 7(10): igad076, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38094937

RESUMEN

Background and Objectives: Rejection of care is common in hospitalized persons living with dementia. However, distinguishing between rejection of care behaviors related to care practices or other causes, such as pain or delirium, is challenging. The purpose of this study is to further understand the relationship between rejection of care and pain and delirium in hospitalized patients with dementia by identifying which rejection of care behaviors are associated with pain and delirium. Research Design and Methods: Care encounters between hospitalized patients with dementia (n = 16) and nursing staff (n = 53) were observed on 88 separate occasions across 35 days. Rejection of care was measured using the 13 behaviors from the Resistiveness to Care Scale. Pain and delirium severity were measured using a variety of scales including the Pain Assessment in Advanced Dementia Scale, Checklist of Nonverbal Pain Indicators, and numeric rating scale for pain severity and the Confusion Assessment Method-Severity short form and Delirium Observation Screening Scale for delirium severity. Linear mixed modeling was used to determine the relationship between rejection of care behaviors and pain and delirium severity for each measure. Results: About 48.9% of the observations included rejection of care, 49.9% included a patient in pain, and 12.5% included a patient with delirium. Cry, push away, scream/yell, and turn away indicated a higher pain severity across pain measures. No rejection of care behaviors were found to indicate delirium severity. Discussion and Implications: Certain rejection of care behaviors may be helpful in identifying pain in hospitalized patients with dementia, suggesting that caregivers should be cognizant of pain when these rejection of care behaviors are present. However, in this sample rejection of care behaviors was not found to be useful for identifying delirium severity in hospital dementia care.

13.
J Pharm Investig ; 52(3): 273-292, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35003824

RESUMEN

Background: Nucleic acid-based gene therapy is a promising technology that has been used in various applications such as novel vaccination platforms for infectious/cancer diseases and cellular reprogramming because of its fast, specific, and effective properties. Despite its potential, the parenteral nucleic acid drug formulation exhibits instability and low efficacy due to various barriers, such as stability concerns related to its liquid state formulation, skin barriers, and endogenous nuclease degradation. As promising alternatives, many attempts have been made to perform nucleic acid delivery using a microneedle system. With its minimal invasiveness, microneedle can deliver nucleic acid drugs with enhanced efficacy and improved stability. Area covered: This review describes nucleic acid medicines' current state and features and their delivery systems utilizing non-viral vectors and physical delivery systems. In addition, different types of microneedle delivery systems and their properties are briefly reviewed. Furthermore, recent advances of microneedle-based nucleic acid drugs, including featured vaccination applications, are described. Expert opinion: Nucleic acid drugs have shown significant potential beyond the limitation of conventional small molecules, and the current COVID-19 pandemic highlights the importance of nucleic acid therapies as a novel vaccination platform. Microneedle-mediated nucleic acid drug delivery is a potential platform for less invasive nucleic acid drug delivery. Microneedle system can show enhanced efficacy, stability, and improved patient convenience through self-administration with less pain.

14.
Arch Pharm Res ; 45(4): 245-262, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35426547

RESUMEN

Synthetic mRNA has been considered as an emerging biotherapeutic agent for the past decades. Recently, the SARS-CoV-2 pandemic has led to the first clinical use of synthetic mRNA. mRNA vaccines showed far surpassing influences on the public as compared to other vaccine platforms such as viral vector vaccines and recombinant protein vaccines. It allowed rapid development and production of vaccines that have never been achieved in history. Synthetic mRNA, called in vitro transcribed (IVT) mRNA, is the key component of mRNA vaccines. It has several advantages over conventional gene-expressing systems such as plasmid DNA and viral vectors. It can translate proteins in the cytoplasm by structurally resembling natural mRNA and exhibit various protein expression patterns depending on how it is engineered. Another advantage is that synthetic mRNA enables fast, scalable, and cost-effective production. Therefore, starting with the mRNA vaccine, synthetic mRNA is now in the spotlight as a promising new drug development agent. In this review, we will summarize the latest IVT mRNA technology such as new mRNA structures or large-scale production. In addition, the nature of the innate immunogenicity of IVT mRNA will be discussed along with its roles in the development of vaccines. Finally, the principles of the mRNA vaccine and the future direction of synthetic mRNA will be provided.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevención & control , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , SARS-CoV-2/genética , Vacunas Sintéticas , Vacunas de ARNm
15.
JMIR Med Educ ; 8(1): e34171, 2022 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-34982035

RESUMEN

BACKGROUND: Given the limitations imposed by the COVID-19 pandemic, a better understanding of how nursing programs around the globe have implemented distance education methods and related initiatives to provide international collaborative learning opportunities as well as complementary aspects of practical education would be constructive for nursing students. It is expected that international collaboratives through web-based communication will continue to be increasingly utilized after the pandemic; therefore, it is time to discuss the effects and direction of these developments. OBJECTIVE: We aimed to examine the impact of an online international collaborative learning program on prelicensure nursing students' international and global competencies in South Korea. METHODS: We conducted a mixed methods study (web-based surveys and focus group interviews). A total of 15 students participated in the study. The surveys were used to examine changes in participants' global leadership competencies, and the focus group interviews were used to evaluate the program's effectiveness and to identify opportunities for improvement. The online international collaborative program consisted of 7 synchronous web-based classroom sessions. Each session ran for 60 to 90 minutes. Faculty experts and nurses working in the United States discussed various topics with students, such as nursing education in the United States and evidence-based teaching and learning. The students gave presentations on the South Korean nursing education system. Data were analyzed with descriptive statistics, the Mann-Whitney U test, and content analysis methods. RESULTS: Participants reported improvement in their global leadership competencies. Four main categories emerged from analysis of the focus interviews: (1) realistic applicability, (2) clarification, (3) expansion of perspectives, and (4) initiative. CONCLUSIONS: The online international collaborative learning program had a positive impact on the development of students' international competencies. The findings support the further development of international exchange programs through web-based meetings in the postpandemic era.

16.
J Control Release ; 343: 57-65, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34763005

RESUMEN

Dicer substrate RNA is an alternative gene silencing agent to canonical siRNA. Enhanced in vitro gene silencing can be achieved with RNA substrates by facilitating Ago2 loading of dsRNA after Dicer processing. However, the in vivo use of Dicer substrate RNA has been hindered by its instability and immunogenicity in the body due to the lack of proper chemical modification in the structure. Here, we report a universal chemical modification approach for Dicer substrate RNA nanostructures by optimizing protein-RNA interactions in the RNAi pathway. Proteins involved in the RNAi pathway were utilized for evaluating their recognition and binding of substrate RNA. It was found that conventional chemical modifications could severely affect the binding and processing of substrate RNA, consequently reducing RNAi activity. Protein-RNA interaction guided chemical modification was introduced to RNA nanostructures, and their gene silencing activity was assessed. The optimized RNA nanostructures showed excellent binding and processability with RNA binding proteins and offered the enhancement of in vivo EC50 up to 1/8 of its native form.


Asunto(s)
Silenciador del Gen , Nanoestructuras , Interferencia de ARN , ARN Bicatenario , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo
17.
Artículo en Inglés | MEDLINE | ID: mdl-36011504

RESUMEN

This study aimed to verify the relationship between handgrip strength and oral health using data from the Korea National Health and Nutrition Examination Survey, representing Korean adults. Data from the seventh survey (2016−2018) conducted by the Korea Centers for Disease Control and Prevention were utilized, and 10,607 final study participants were recruited according to the selection and exclusion criteria. A complex sample logistic regression analysis was performed to confirm the relationship between handgrip strength and dental caries according to the sex of the study participants. On analyzing the correlation in men, "C1 (DMFT: 11−32)," when compared to "C4 (DMFT: 0−3)," in Model 1 without adjustment for potential confounders, was 2.92 (95% confidence interval [CI]: 2.15−3.97) times more likely to be associated with lower handgrip strength, and a statistically significant result was detected (p < 0.001). Additionally, significant odds ratios (ORs) were confirmed for all adjusted models. In women, the ORs in Model 1 without adjustment for potential confounders were 1.41 times (95% CI: 1.14−1.75) and demonstrated a significant result; however, the results were not significant in all adjusted models 2−4. Resultantly, a significant association was detected between dental caries and handgrip strength in Korean adults.


Asunto(s)
Caries Dental , Fuerza de la Mano , Adulto , Estudios Transversales , Caries Dental/epidemiología , Femenino , Humanos , Masculino , Encuestas Nutricionales , República de Corea/epidemiología
18.
Artículo en Inglés | MEDLINE | ID: mdl-33652984

RESUMEN

This study aimed to identify educational needs and determine priorities in nursing care for home visit nurses providing services within the national long-term care insurance system in South Korea. This cross-sectional descriptive study assessed the educational needs of 92 home visit nurses. Participants' characteristics were analyzed using percentages, averages, and standard deviations. Educational needs were calculated for participants' current and required competency levels, utilizing the paired t-test, Borich's educational needs formula, and the locus for focus model. Four main categories were identified as top priorities: (1) health assessment, (2) cognitive function care, (3) disease management, and (4) medication management. The study's findings could support the development of appropriate and responsive education and training programs for home-visit nurses-as it reflects the actual needs of this group.


Asunto(s)
Visita Domiciliaria , Seguro de Cuidados a Largo Plazo , Estudios Transversales , Femenino , Humanos , Atención Posnatal , Embarazo , República de Corea
19.
Artículo en Inglés | MEDLINE | ID: mdl-34639409

RESUMEN

This paper reports a scoping review of the literature on eating difficulties among older adults with dementia in long-term care facilities to identify key concepts, methods of measuring outcomes, interventions, and related factors. A scoping review was performed using the bibliographic databases PubMed, CINAHL, PsycINFO, and Cochrane Library. A combination of keywords and subject headings related to eating or feeding difficulties was used. Inclusion criteria were limited to materials published in English. A total of 1070 references were retrieved, of which 39 articles were selected after applying the inclusion and exclusion criteria. Articles that met the criteria were published between 1987 and 2020. "Eating disabilities" have been defined as problems related to choosing food and/or the ability to get food to one's mouth, chew, and swallow. Interventions for eating difficulties described in the literature include spaced retrieval training, Montessori training, and feeding skill training. Intrapersonal, interpersonal, and environmental factors related to eating difficulties were identified. This scoping review will provide direct care workers, nursing educators, and administrators with an overview of eating performance and a broad understanding of eating difficulties for older adults with dementia in long-term care facilities.


Asunto(s)
Demencia , Cuidados a Largo Plazo , Anciano , Demencia/epidemiología , Instituciones de Salud , Humanos , Evaluación de Resultado en la Atención de Salud , Instituciones de Cuidados Especializados de Enfermería
20.
Int J Pharm ; 606: 120940, 2021 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-34310959

RESUMEN

The tissue-specific targeted delivery and efficient cellular uptake of siRNAs are the main obstacles to their clinical application. Antibody-siRNA-conjugates (ARCs) can deliver siRNA by exploiting the targeting property of antibodies like antibody-drug conjugates (ADCs). However, the effective conjugation of antibodies and siRNAs and the release of siRNAs specifically at target sites have posed challenges to the development of ARCs. In this study, the successful conjugation of antibodies and siRNAs was achieved using a multifunctional peptide as a linker, composed of a cell-penetrating peptide (CPP) and a substrate peptide (SP), which is highly expressed in solid tumors. The resulting antibody-multifunctional peptide (SP-CPP)-siRNA system delivered the siRNA to target tumor cells by the specific binding of the antibody. Once the enzymes on the tumor cell surface hydrolyzed the substrate peptide linker, siRNA-CPP was released from ARCs. The released siRNA-CPP entered the targeted cells via the cellular penetrating ability of CPP, resulting in improved siRNA-mediated gene silencing efficiency, verified both in vitro and in vivo. After intravenous administration, the designed ARCs achieved approximately 66.7% EGFP (Enhanced Green Fluorescent Protein) downregulation efficiency in nude mice xenografted with the HCT116-EGFP tumor model. The proposed system provides a prospective choice for ARC production and the safe and efficient delivery of siRNAs.


Asunto(s)
Péptidos de Penetración Celular , Inmunoconjugados , Animales , Línea Celular Tumoral , Ratones , Ratones Desnudos , Estudios Prospectivos , ARN Interferente Pequeño
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